In this mentored clinical scientist training application, the applicant will test the hypothesis that heat shock protein (Hsp) 72 binds to both mitochondria and microtubules stabilizing them;thus making this complex resistant to exogenous insult and thereby preventing apoptosis in the intestinal epithelium and uncovering future avenues for the prevention of necrotizing eneterocolitis (NEC). The preliminary data strongly support this hypothesis. The studies outlined in this application are aimed at examining the specific mechanism(s) of the relationship between protection and the complex interaction between the mitochondria and microtubular network. These investigations will provide an excellent training opportunity in the areas of epithelial biology, confocal microscopy and the acquisition of techniques needed to apply the cellular observations to the whole animal. The applicant, Jennifer L. Liedel, MD, will complete fellowships in neonatology and pediatric critical care at the University of Chicago June 30, 2004. In 2000, during the first year of her four-year training period, she formally entered the laboratory of Dr. Eugene Chang to seek additional basic science training and to study the effects of heat shock proteins in protection of the intestinal epithelium and the prevention of apoptosis. The proposed training plan provides 75% protected time, exceptional opportunities to acquire new skills and experience in the areas of cellular and molecular biology as well as didactic training in techniques and proper research conduct. This plan also provides meaningful interactions with experienced investigators, allowing the applicant to mature into a successful independent investigator. The applicant's research will form a solid foundation upon which the future direction and research necessary to build a career in academic medicine can be based.